Pawankar R, Okuda M, Yssel H, Okumura K, Ra C
Department of Immunology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan.
J Clin Invest. 1997 Apr 1;99(7):1492-9. doi: 10.1172/JCI119311.
Cross-linking of allergen specific IgE bound to the high affinity IgE receptor (FC epsilonRI) on the surface of mast cells with multivalent allergens results in the release of both pre-formed and newly generated mediators, and in the manifestation of allergic symptoms. The expression of Fc epsilonRI, and the synthesis of IgE are therefore critical for the development of allergic diseases. In this study, we report that nasal mast cells (NMC) from patients with perennial allergic rhinitis (PAR) expressed significantly greater levels of the Fc epsilonRI, CD40L, IL-4, and IL-13 as compared to NMC from patients with chronic infective rhinitis (CIR). The level of Fc epsilonRI expression in NMC of PAR patients strongly correlated with the levels of serum total (r = 0.8, P < 0.003) and specific IgE (r = 0.89, P < 0.0004) antibodies. In addition, stimulation of NMC with IL-4, upregulated the Fc epsilonRIalpha chain expression both at the protein and mRNA levels, as detected by flow cytometry and reverse transcriptase-polymerase chain reaction. Furthermore, NMC from PAR, but not CIR, patients induced IgE synthesis by purified B cells in the presence of Der fII (mite antigen). These results suggest novel and critical roles for mast cells in promoting the allergic reaction through the increased expression of Fc epsilonRI and by enhancing and amplifying the IgE production, within the local microenvironment.
多价变应原与肥大细胞表面高亲和力IgE受体(FcεRI)上结合的变应原特异性IgE发生交联,会导致预先形成的介质和新生成的介质释放,进而引发过敏症状。因此,FcεRI的表达以及IgE的合成对于过敏性疾病的发展至关重要。在本研究中,我们报告称,与慢性感染性鼻炎(CIR)患者的鼻肥大细胞(NMC)相比,常年性变应性鼻炎(PAR)患者的NMC表达的FcεRI、CD40L、IL-4和IL-13水平显著更高。PAR患者NMC中FcεRI的表达水平与血清总IgE(r = 0.8,P < 0.003)和特异性IgE(r = 0.89,P < 0.0004)抗体水平密切相关。此外,用IL-4刺激NMC后,通过流式细胞术和逆转录聚合酶链反应检测发现,FcεRIα链在蛋白质和mRNA水平上的表达均上调。此外,PAR患者而非CIR患者的NMC在存在Der fII(螨抗原)的情况下能诱导纯化的B细胞合成IgE。这些结果表明,肥大细胞在局部微环境中通过增加FcεRI的表达以及增强和放大IgE的产生,在促进过敏反应中发挥着新的关键作用。